6-85507915-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_153816.6(SNX14):c.2745+53G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,419,042 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (28 hom., cov: 31)
  • Exomes 𝑓: 0.0013 (26 hom.)
• Consequence: SNX14 NM_153816.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.243

Genes affected

SNX14 (HGNC:14977): (sorting nexin 14) This gene encodes a member of the sorting nexin family. Members of this family have a phox (PX) phosphoinositide binding domain and are involved in intracellular trafficking. The encoded protein also contains a regulator of G protein signaling (RGS) domain. Regulator of G protein signaling family members are regulatory molecules that act as GTPase activating proteins for G alpha subunits of heterotrimeric G proteins. Alternate splicing results in transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-85507915-C-T is Benign according to our data. Variant chr6-85507915-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1208139.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0112 (1708/152190) while in subpopulation AFR AF= 0.0384 (1594/41502). AF 95% confidence interval is 0.0368. There are 28 homozygotes in gnomad4. There are 826 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX14	NM_153816.6	c.2745+53G>A		intron_variant		ENST00000314673.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX14	ENST00000314673.8	c.2745+53G>A		intron_variant		1	NM_153816.6	P4

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1707 AN: 152072 Hom.: 28 Cov.: 31

Gnomad AFR AF: 0.0385

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00426

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00908

GnomAD4 exome AF: 0.00131 AC: 1658 AN: 1266852 Hom.: 26 AF XY: 0.00110 AC XY: 704 AN XY: 639768

Gnomad4 AFR exome AF: 0.0403

Gnomad4 AMR exome AF: 0.00279

Gnomad4 ASJ exome AF: 0.00143

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000249

Gnomad4 FIN exome AF: 0.000173

Gnomad4 NFE exome AF: 0.000197

Gnomad4 OTH exome AF: 0.00227

GnomAD4 genome AF: 0.0112 AC: 1708 AN: 152190 Hom.: 28 Cov.: 31 AF XY: 0.0111 AC XY: 826 AN XY: 74410

Gnomad4 AFR AF: 0.0384

Gnomad4 AMR AF: 0.00425

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.000708 Hom.: 0

Bravo AF: 0.0138

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.1
Dann	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs61749066; hg19: chr6-86217633;